scholarly journals Prognostic Value of TRPM7 Expression and Factor XIIIa-Expressing Tumor-Associated Macrophages in Gastric Cancer

2021 ◽  
Vol 2021 ◽  
pp. 1-25
Author(s):  
Muhammet Calik ◽  
Ilknur Calik ◽  
Gokhan Artas ◽  
Ibrahim Hanifi Ozercan

Purpose. TRPM7 is known to play a key role in tumor progression by regulating cellular proliferation, migration, and invasion in various cancer cell lines. However, there are no comprehensive clinical studies about the effect of TRPM7 expression on gastric cancer (GC) prognosis. In this study, it was aimed at investigating the effect of TRPM7 expression on prognosis in GC patients. Additionally, for the first time, it was investigated whether the density of Factor XIIIa-expressing tumor-associated macrophages (TAMs) in GC has an effect on the biological behaviour of the tumor. Methods. TRPM7 expression and Factor XIIIa-expressing TAM density were immunohistochemically evaluated in paraffin-embedded tumor tissues of 204 GC patients undergoing surgery at a single institution. Results. Tumor size was clearly higher in cases with high TRPM7 expression than those with low expression ( p < 0.001 , Mann-Whitney U ). TRPM7 overexpression was closely related to high depth of tumor invasion ( p < 0.001 , ANOVA), increased lymph node metastasis ( p < 0.001 , ANOVA), and high distant metastasis rate ( p < 0.001 , Mann-Whitney U ). These findings exposed that high TRPM7 expression is effective in the progression and aggressiveness of GC. In addition, while high CD8+ TIL density affects the prognosis positively, it was determined that high Factor XIIIa+ TAM density negatively affects the prognosis of patients with GC. Furthermore, multivariate analyses revealed TRPM7 overexpression was independently related with short overall (HR 9.64, 95% CI 5.74–16.19, p < 0.001 ) and disease-free survival (HR 5.67, 95% CI 3.61-8.92, p < 0.001 ) in GC patients. Conclusions. Our data suggest that high TRPM7 expression is closely related to progressive tumor behaviour in GC and independently negatively affects survival in patients. In addition, it was determined that a high density of Factor XIIIa+ TAMs negatively affects the prognosis of patients with GC.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 50-50 ◽  
Author(s):  
Keon-Woo Park ◽  
Hyuk-Chan Kwon ◽  
Su-Jin KIm ◽  
Hyung-Sik Lee

50 Background: Nuclear factor-κB (NF-κB) and vascular endothelial growth factor (VEGF) are involved in cell proliferation, invasion, angiogenesis and metastases. The principal objective of this study was to assess the prognostic significance of NF-κB and VEGF expression in gastric cancer Methods: The tumor tissues of 154 patients with gastric cancer, all of whom underwent potentially curative resection, were immunohistochemically evaluated using monoclonal antibodies against NF-κB and VEGF. Results: Positivity rates of NF-κB and VEGF were 44.2% and 39.6%, respectively. NF-κB expression in tumor tissues was correlated significantly with VEGF expression (p < 0.001). VEGF expression was related to Lauren’s classification (p = 0.002), differentiation (p = 0.043), depth of invasion (p = 0.005), carcinoembryonic antigen (p = 0.032), and stage (p = 0.026). However, NF-κB expression was not related to any of these parameters. Univariate analysis demonstrated that NF-κB expression was significantly related with both 5-year disease free survival (65.2% vs. 46.4%, p = 0.007), and 5-year overall survival (60.0% vs. 42.5%, p = 0.014). Multivariate analysis verified that NF-κB was independently associated with disease free survival (hazard ratio: 2.082, p = 0.005), and overall survival (hazard ratio: 1.841, p = 0.008). However, VEGF did not appear to be related to adverse clinical outcome. Conclusions: NF-κB expression in tumor tissue is associated with poor survival in gastric cancer patients.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Mahdieh Razmi ◽  
Roya Ghods ◽  
Somayeh Vafaei ◽  
Maryam Sahlolbei ◽  
Leili Saeednejad Zanjani ◽  
...  

Abstract Background Gastric cancer (GC) is considered one of the most lethal malignancies worldwide, which is accompanied by a poor prognosis. Although reports regarding the importance of cancer stem cell (CSC) markers in gastric cancer progression have rapidly developed over the last few decades, their clinicopathological and prognostic values in gastric cancer still remain inconclusive. Therefore, the current meta-analysis aimed to quantitatively re-evaluate the association of CSC markers expression, overall and individually, with GC patients’ clinical and survival outcomes. Methods Literature databases including PubMed, Scopus, ISI Web of Science, and Embase were searched to identify the eligible articles. Hazard ratios (HRs) or odds ratios (ORs) with 95% confidence intervals (CIs) were recorded or calculated to determine the relationships between CSC markers expression positivity and overall survival (OS), disease-free survival (DFS)/relapse-free survival (RFS), disease-specific survival (DSS)/ cancer-specific survival (CSS), and clinicopathological features. Results We initially retrieved 4,425 articles, of which a total of 66 articles with 89 studies were considered as eligible for this meta-analysis, comprising of 11,274 GC patients. Overall data analyses indicated that the overexpression of CSC markers is associated with TNM stage (OR = 2.19, 95% CI 1.84–2.61, P = 0.013), lymph node metastasis (OR = 1.76, 95% CI 1.54–2.02, P < 0.001), worse OS (HR = 1.65, 95% CI 1.54–1.77, P < 0.001), poor CSS/DSS (HR = 1.69, 95% CI 1.33–2.15, P < 0.001), and unfavorable DFS/RFS (HR = 2.35, 95% CI 1.90–2.89, P < 0.001) in GC patients. However, CSC markers expression was found to be slightly linked to tumor differentiation (OR = 1.25, 95% CI 1.01–1.55, P = 0.035). Sub-analysis demonstrated a significant positive relationship between most of the individual markers, specially Gli-1, Oct-4, CD44, CD44V6, and CD133, and clinical outcomes as well as the reduced survival, whereas overexpression of Lgr-5, Nanog, and sonic hedgehog (Shh) was not found to be related to the majority of clinical outcomes in GC patients. Conclusion The expression of CSC markers is mostly associated with worse outcomes in patients with GC, both overall and individual. The detection of a combined panel of CSC markers might be appropriate as a prognostic stratification marker to predict tumor aggressiveness and poor prognosis in patients with GC, which probably results in identifying novel potential targets for therapeutic approaches.


2014 ◽  
Vol 31 (7) ◽  
Author(s):  
Xiao-tian Ye ◽  
Ai-jun Guo ◽  
Peng-fei Yin ◽  
Xian-dong Cao ◽  
Jia-cong Chang

2021 ◽  
Vol 2021 ◽  
pp. 1-19
Author(s):  
Zhihuai Wang ◽  
Shuai Chen ◽  
Gaochao Wang ◽  
Sun Li ◽  
Xihu Qin

Cell division cycle-associated protein-3 (CDCA3) contributes to the regulation of the cell cycle. CDCA3 plays an important role in the carcinogenesis of various cancers; however, the association between CDCA3 expression, prognosis of patients, and immune infiltration in the tumor microenvironment is still unknown. Here, we demonstrated that CDCA3 was differentially expressed between the tumor tissues and corresponding normal tissues using in silico analysis in the ONCOMINE and Tumor Immune Estimation Resource (TIMER) databases. We analyzed the relationship between the expression of CDCA3 and prognosis of patients with hepatocellular carcinoma (HCC) using the Kaplan–Meier plotter database and Gene Expression Profiling Interactive Analysis (GEPIA). Furthermore, we determined the prognostic value of CDCA3 expression using univariate and multivariate analyses. We observed that CDCA3 expression closely correlated with immune infiltration and gene markers of infiltrating immune cells in the TIMER database. CDCA3 was highly expressed in the tumor tissues than in the adjacent normal tissues in various cancers, including HCC. Increased expression of CDCA3 was accompanied by poorer overall survival (OS), relapse-free survival (RFS), progression-free survival (PFS), and disease-specific survival (DSS). The correlation between CDCA3 expression and OS and disease-free survival (DFS) was also studied using GEPIA. CDCA3 expression was associated with the levels of immune cell infiltration and was positively correlated with tumor purity. Moreover, CDCA3 expression was associated with gene markers such as PD-1, CTLA4, LAG3, and TIM-3 from exhausted T cells, CD3D, CD3E, and CD2 from T cells, and TGFB1 and CCR8 located on the surface of Tregs. Thus, we demonstrated that CDCA3 may be a potential target and biomarker for the management and diagnosis of HCC.


2014 ◽  
Vol 21 (6) ◽  
pp. 1998-2004 ◽  
Author(s):  
Paolo Aurello ◽  
Simone Maria Tierno ◽  
Giammauro Berardi ◽  
Federico Tomassini ◽  
Paolo Magistri ◽  
...  

2018 ◽  
Vol 38 (6) ◽  
Author(s):  
Jingjing Zhang ◽  
Jun Xu ◽  
Yonghong Dong ◽  
Bo Huang

In view of the high incidence of gastric cancer and the functions of hypoxia-inducible factor 1α (HIF-1α), our study aimed to investigate the functionality of HIF-1α in gastric cancer, and to explore the diagnostic and prognostic values of HIF-1α for this disease. Expression of HIF-1α in tumor tissues and adjacent healthy tissues as well as serum collected from both gastric cancer patients and normal healthy controls was detected by qRT-PCR. Survival analysis was performed using Kaplan–Meier method. HIF-1α siRNA silencing cell lines were established. Effects of HIF-1α siRNA silencing as well as PI3K activator sc3036 on proliferation, migration, and invasion of gastric cancer cells were detected by Cell counting kit (CCK-8) assay, and Transwell migration and invasion assay. Effects of HIF-1α siRNA silencing on AKT and VEGF were detected by Western blot. Expression of HIF-1α was significantly down-regulated in tumor tissues than in adjacent healthy tissues in most gastric cancer patients. Serum levels of HIF-1α were also higher in gastric cancer patients than in normal healthy people. Serum HIF-1α showed promising diagnostic and prognostic values for gastric cancer. HIF-1α siRNA silencing inhibited the proliferation, migration, and invasion of gastric cancer cells, while PI3K activator sc3036 treatment reduced those inhibitory effects. Down-regulation of HIF-1α can inhibit the proliferation, migration, and invasion of gastric cancer possibly by inhibiting PI3K/AKT pathway and VEGF expression.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jing Guo ◽  
Aman Xu ◽  
Xiaowei Sun ◽  
Xuhui Zhao ◽  
Yabin Xia ◽  
...  

AbstractWhether extensive intraoperative peritoneal lavage (EIPL) after gastrectomy is beneficial to patients with locally advanced gastric cancer (AGC) is not clear. This phase 3, multicenter, parallel-group, prospective randomized study (NCT02745509) recruits patients between April 2016 and November 2017. Eligible patients who had been histologically proven AGC with T3/4NxM0 stage are randomly assigned (1:1) to either surgery alone or surgery plus EIPL. The results of the two groups are analyzed in the intent-to-treat population. A total of 662 patients with AGC (329 patients in the surgery alone group, and 333 in the surgery plus EIPL group) are included in the study. The primary endpoint is 3-year overall survival (OS). The secondary endpoints include 3-year disease free survival (DFS), 3-year peritoneal recurrence-free survival (reported in this manuscript) and 30-day postoperative complication and mortality (previously reported). The trial meets pre-specified endpoints. Estimated 3-year OS rates are 68.5% in the surgery alone group and 70.6% in the surgery plus EIPL group (log-rank p = 0.77). 3-year DFS rates are 61.2% in the surgery alone group and 66.0% in the surgery plus EIPL group (log-rank p = 0.24). The pattern of disease recurrence is similar in the two groups. In conclusion, EIPL does not improve the 3-year survival rate in AGC patients.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16019-e16019
Author(s):  
Zhili Shan ◽  
Feng Guo ◽  
Hong Chen ◽  
Dapeng Li ◽  
Zhongqi Mao ◽  
...  

e16019 Background: Postoperative adjuvant chemotherapy is commonly given after the curative resection of gastric cancer (GC) in both Eastern and Western countries. Several studies have investigated the feasibility and safety of S-1 plus docetaxel or S-1 plus cisplatin. However, the best choice of adjuvant treatment for patients with gastric cancer is still debated. Apatinib, an oral small molecular of VEGFR-2 TKI, has been confirmed to improve OS and PFS with acceptable safety profile in patients with advanced gastric cancer refractory to two or more lines of prior chemotherapy. In this study, we aimed to evaluate the efficacy and safety of apatinib combined with S-1/docetaxel for locally advanced gastric cancer (T3-4aN+M0). Methods: This is a prospective, randomized, controlled, multicenter clinical study. Patients with locally advanced gastric cancer, pathological stage T3-4aN+M0 who underwent D2 lymphadenectomy without prior anti-cancer therapy were included. All these patients were assigned to group A or B. Patients in group A received 6 cycles (21 days a cycle) of adjuvant therapy using S-1 (80-120mg/d, d1-14), and docetaxel (40mg/m2, d1). Group B received the same regimen with the addition of apatinib (250mg, qd.). The primary endpoint was disease-free survival (DFS). The final analysis cutoff date was 30 November, 2020. Results: A total of 45 patients were enrolled from January 2019 to November, 2010 and assigned to group A (21) or group B (24). The DFS was not reached in both of the groups. The 1-year disease-free survival rate was 60% in group A and 90% in the group B, while the difference was not significant. The main AEs in group A were anemia (55%), nausea (50%) and neutropenia (40%); The most common AEs in group B were anemia (45%) neutropenia (40%) and diarrhea (25%). There were no treatment-related deaths. The longest administered time of apatinib with no progression was 457 days. And the median time to receive apatinib was 329 days. Conclusions: Combination of apatinib with S-1/docexal chemotherapy shows clinical benefits in locally advanced gastric cancer (T3-4aN+M0), with tolerable toxicity. The study is still ongoing to reach our final endpoint, DFS. Clinical trial information: ChiCTR2000038900.


2019 ◽  
Vol 05 (02) ◽  
pp. 072-074
Author(s):  
Sajal Goel ◽  
Deepak K. Mittal ◽  
Pankaj Sharma ◽  
Nita Khurana

Abstract Introduction Pleomorphic sarcoma is the commonest soft tissue sarcoma of adult life. Less than 10% cases of this disease occur as primary in head and neck region. Although a case of pleomorphic sarcoma of lower extremity with metastasis to base of tongue had been reported earlier, a pleomorphic sarcoma arising from oropharynx is being reported for the first time. Case Report A 75-year-old male chronic smoker was evaluated for complaints of dysphagia, change in voice, and multiple episodes of oral bleeding. He was found to have a locally advanced pleomorphic sarcoma of oropharynx. He was treated nonsurgically. He showed complete clinical and radiologic response. The disease-free survival is 12 months and overall survival is 74 months. Conclusion This report highlights the importance of nonsurgical management of a case that would have otherwise needed surgery.


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